Antidiabetic Drugs and their Potential Use in COVID-19: A Mechanistic Approach

Many therapies have been developed against COVID-19 since it first appeared in December 2019. Antivirals, antimalarials, cephalosporins, colchicine, anticoagulants, and corticosteroids, among others, have been evaluated as protecting agents against antibacterial complications due to their anti-inflammatory and immunomodulatory effects against thrombosis and cell death caused by infection with SARS-CoV-2. Nevertheless, the overall balance in their application has not been found to be satisfactory. On the other hand, developing and applying several vaccines against this virus have marked an important watershed in preventive and prophylactic medicine in the new millennium. However, given the regular efficacy reported of some of them, the still scarce affordability, and the emergency of new strains for which no drug has been evaluated, the search for new pharmacological therapy alternatives still represents an essential component in the clinical management of COVID-19, and the rapid identification of drugs with potential antiviral and/or immunomodulatory properties is needed. In the present review, a potential therapeutic effect of metformin and other antidiabetic therapies for the management of COVID-19 are proposed and discussed from the viewpoint of their in vitro and in vivo immunomodulatory effects. Given that acute inflammation is an important component of COVID-19, antidiabetic therapies could be promising alternatives in its management and reducing the disease's severity. In order to understand how metformin and other antidiabetic therapies could work in the context of COVID-19, here we review the possible mechanisms of action through a detailed description of cellular and molecular events.